The distribution of cholecystokinin octapeptide-like structures in the lower brain stem of the rat: An immunohistochemical analysis

Kubota, Yoshihiro; Inagaki, Shinobu; Shiosaka, Sadao; Cho, H.J.; Tateishi, Kensuke; Hashimura, E.; Hamaoka, Toshiyuki; Tohyama, Masaya

doi:10.1016/0306-4522(83)90176-8

Cited by 113 publications

(40 citation statements)

References 47 publications

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“…Why peripheral type receptors should be present in other areas such as the IPN is unclear, as, in contrast to the AP, the IPN is located well within the blood-brain barrier. CCK-like im-munoreactivity is present in cell bodies located on the rostra1 margins of the nucleus, and dense networks of fiber plexi, which also show CCK-like immunoreactivity, can be detected surrounding the IPN (Kubota et al, 1983;Hamill et al, 1984). However, the density of these is much less within the nucleus itself.…”

Section: Discussionmentioning

confidence: 93%

“…Indeed, as the sulfated octapeptide (sCCK-8), it is found in certain brain regions in higher concentrations than any other neuropeptide (see Crawley, 1985, for review). The distribution of sCCK-8 throughout the CNS, its localization in neuronal perikarya and nerve fibers, and its coexistence with other putative neurotransmitters (HBkfelt et al, 1980;Greenwood et al, 198 1;Vanderhaeghan et al, 198 1;Kubota et al, 1983;Hamill et al, 1984) suggest that this peptide may act as either a neurotransmitter or a neuromodulator. Additionally, the demonstration of binding sites with high affinity for sCCK-8 and related peptide fragments throughout the brain further supports the notion that sCCK-8 might be considered as an important mediator of information transfer between neurons.…”

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confidence: 99%

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Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists

Hill¹,

Campbell²,

Shaw³

et al. 1987

J. Neurosci.

314

104

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Two potent and highly selective nonpeptide antagonists, L-365,031 [1- methyl-3-(4-bromobenzoyl)amino-5-phenyl-3H-1,4 benzodiazepin-2-one] and 3H-L-364,718 [1-methyl-3-(2-indoloyl)amino-5-phenyl-3H-1,4 benzodiazepin-2-one] were used to localize “peripheral” CCK receptors in rat brain. In autoradiographic experiments, L-365,031 displaced 125I- Bolton Hunter CCK-8 binding from the interpeduncular nucleus (IPN) (IC50 = 7 X 10(-8) M), the area postrema (AP), and the nucleus tractus solitarius (NTS) without influencing specific binding to other areas, such as the cerebral cortex or the spinal tract of the trigeminal nerve. Desulfated CCK preferentially inhibited 125I-CCK binding to cerebral cortex (IC50 = 7 X 10(-8) M) rather than IPN (IC50 greater than 1 X 10(-6) M) or AP-NTS. In the medulla the localization of 3H-L- 364,718 binding was similar to L-365,031-sensitive 125I-CCK-8 binding and was found in the AP and medial, but not lateral, aspects of the NTS. In membranes prepared from IPN, NTS, and AP, 3H-364,718 binding was of high affinity (Kd = 0.14 nM), saturable (Bmax = 20 fmol/mg protein), and inhibited by compounds previously shown to act at pancreatic CCK receptors. The receptors labeled by 3H-364,718 were modulated by guanyl nucleotide, which reduced agonist affinity 10-fold without affecting antagonist binding. The localization and high density of CCK receptors in AP and NTS suggest that these receptors may play an important role in processing sensory afferent information.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists

Hill¹,

Campbell²,

Shaw³

et al. 1987

J. Neurosci.

314

104

View full text Add to dashboard Cite

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“…One possibility is that CCK originates from local peptide-containing interneurons; indeed, CCK is one the most widespread neuropeptides in the brain, and there is abundant neurochemical evidence showing the presence of both CCK receptors, as well as CCK-containing neurons and terminals in the caudal brain stem (15,16,22,31,57,65), suggesting that local neurons containing CCK may also contribute to its effects in vagal brain stem circuits.…”

Section: Discussionmentioning

confidence: 99%

Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats

Baptista¹,

Browning²,

Travagli³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Baptista V, Browning KN, Travagli RA. Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats. Am J Physiol Regul Integr Comp Physiol 292: R1092-R1100, 2007. First published November 22, 2006; doi:10.1152/ajpregu.00517.2006.-We have shown recently that cholecystokinin octapeptide (CCK-8s) increases glutamate release from nerve terminals onto neurons of the nucleus tractus solitarius pars centralis (cNTS). The effects of CCK on gastrointestinal-related functions have, however, been attributed almost exclusively to its paracrine action on vagal afferent fibers. Because it has been reported that systemic or perivagal capsaicin pretreatment abolishes the effects of CCK, the aim of the present work was to investigate the response of cNTS neurons to CCK-8s in vagally deafferented rats. In surgically deafferented rats, intraperitoneal administration of 1 or 3 g/kg CCK-8s increased c-Fos expression in cNTS neurons (139 and 251% of control, respectively), suggesting that CCK-8s' effects are partially independent of vagal afferent fibers. Using whole cell patch-clamp techniques in thin brain stem slices, we observed that CCK-8s increased the frequency of spontaneous and miniature excitatory postsynaptic currents in 43% of the cNTS neurons via a presynaptic mechanism. In slices from deafferented rats, the percentage of cNTS neurons receiving glutamatergic inputs responding to CCK-8s decreased by ϳ50%, further suggesting that central terminals of vagal afferent fibers are not the sole site for the action of CCK-8s in the brain stem. Taken together, our data suggest that the sites of action of CCK-8s include the brain stem, and in cNTS, the actions of CCK-8s are not restricted to vagal central terminals but that nonvagal synapses are also involved. brain stem; electrophysiology; c-fos CHOLECYSTOKININ, WHICH IS released from intestinal cells following ingestion of nutrients (34,37,47), has profound effects on gastrointestinal functions. In fact, it is well known that cholecystokinin, and, in particular, the cleaved octapeptide cholecystokinin-8s (CCK-8s), induces vagally mediated gastric relaxation, increases pancreatic exocrine secretion, and induces short-term satiety (36,38,41,42,48,62).Many studies have proposed that the vagally mediated effects of CCK-8s are almost exclusively due to a paracrine action of CCK-8s on peripheral, capsaicin-sensitive vagal afferent fibers (8,14,41). This postulate stems mainly from the observations that C-fiber ablation induced by perivagal capsaicin treatment greatly attenuates, or abolishes altogether, the effects of systemic administration of CCK-8s on gastric motility, gastric acid secretion, and pancreatic exocrine secretion (32,33,41,58). One must keep in mind, however, that the localized perineural application involves the use of very high concentrations of capsaicin, usually 33 mM (i.e., 1% solution) (9,23,25,41,56,63,67). Such a high concentration of capsaicin raises the possibility that its observed effects are due to the toxic effects of massiv...

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“…Neurons of the nucleus incertus contain GABA and a range of peptides, such as cholecystokinin, neurotensin, neuromedin B and atrial natriuretic peptide (Kubota et al, 1983;Olucha-Bordonau et al, 2003;Ryan et al, 1995) (see Ryan et al, 2011 for review). Recent studies have revealed that a large population of nucleus incertus neurons express high levels of the peptide, relaxin-3 (RLN3), which is primarily expressed in this region, in addition to smaller adjacent tegmental and midbrain cell groups Bathgate et al, 2003;Tanaka et al, 2005;Ma et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

Olucha-Bordonau¹,

Otero-García²,

Sánchez-Pérez³

et al. 2012

J of Comparative Neurology

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Neural tracing studies have revealed that the rat medial and lateral septum are targeted by ascending projections from the nucleus incertus, a population of tegmental GABA neurons. These neurons express the relaxin‐family peptide, relaxin‐3, and pharmacological modulation of relaxin‐3 receptors in medial septum alters hippocampal theta rhythm and spatial memory. In an effort to better understand the basis of these interactions, we have characterized the distribution of relaxin‐3 fibers/terminals in relation to different septal neuron populations identified using established protein markers. Dense relaxin‐3 fiber plexuses were observed in regions of medial septum containing hippocampal‐projecting choline acetyltransferase (ChAT)‐, neuronal nitric oxide synthase (nNOS)‐, and parvalbumin (PV)‐positive neurons. In lateral septum (LS), relaxin‐3 fibers were concentrated in the ventrolateral nucleus of rostral LS and the ventral nucleus of caudal LS, with sparse labeling in the dorsolateral and medial nuclei of rostral LS, dorsal nucleus of caudal LS, and ventral portion nuclei. Relaxin‐3 fibers were also observed in the septofimbrial and triangular septal nuclei. In the medial septum, we observed relaxin‐3‐immunoreactive contacts with ChAT‐, PV‐, and glutamate decarboxylase‐67‐positive neurons that projected to hippocampus, and contacts between relaxin‐3 terminals and calbindin‐ and calretinin‐positive neurons. Relaxin‐3 colocalized with synaptophysin in nerve terminals in all septal areas, and ultrastructural analysis revealed these terminals were symmetrical and contacted spines, somata, dendritic shafts, and occasionally other axonal terminals. These data predict that this GABA/peptidergic projection modulates septohippocampal activity and hippocampal theta rhythm related to exploratory navigation, defensive and ingestive behaviors, and responses to neurogenic stressors. J. Comp. Neurol. 520:1903–1939, 2012. © 2011 Wiley Periodicals, Inc.

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The distribution of cholecystokinin octapeptide-like structures in the lower brain stem of the rat: An immunohistochemical analysis

Cited by 113 publications

References 47 publications

Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists

Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists

Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

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